Mycobacteria and related microorganisms like nocardia and corynebacteria are still major causes of difficult to treat infections worldwide. Tuberculosis, leprosy, nocardiosis and diphtheria are among others the most important infections to be mentioned. (for example see in: Infectious Diseases, Gorbach, Bartlett, Blacklow (eds), Saunders 1992, pages 1238-1245, 1429-1434, 1622-1626, 1246-1265, 1882-1885). Different antibiotics with various targets are in use, without solving completely the therapeutic problem. Lipases are not among the targets of the common antibiotics in use, although for Mycobacterium tuberculosis lipases and esterases have been reported, which are structurally related to the well known hormone-sensitive lipase family (Chahinian et al., Biochimica et Biophysica Acta 1738 (2005) 29-36, Canaan et al., Eur. J. Biochem., 271, 3953-3961, (2004), Deb et al., J. Biol. Chem., 281, 3866-3875, 2006).
Cyclipostins are known compounds which can be produced by fermentation of Streptomyces sp. HAG 004107 (DSM 13381) as described by Vertesy et al. in PCT patent application WO 0183497 and have previously been described as having medicinal properties by inhibiting hormone sensitive lipase, a key enzyme of hormone metabolism (Vertesy et al., Journal of Antibiotics 2002, 55, 480-494).
Recent developments in antimycobacterial small-molecule therapeutics are e.g. described by van Daele & van Calenberg in Expert Opin. Ther. Patents 2005, 15(2), 131-140. Mycobacteria tend to develop resistances against standard antibiotics such as isoniazid, rifampicin, streptomycin, pyrazinamid and ethambutol. 20% of the tuberculosis infections worldwide are due to multi-resistant strains, with an increase of resistance of 50% in Germany since 1995. It is therefore an object of the present invention to provide an alternative method for the treatment of mycobacterial infections.